No abstract

Computational modeling of the spontaneous dynamics over the whole brain provides critical insight into the spatiotemporal organization of brain dynamics at multiple resolutions and their alteration to changes in brain structure (e.g. in diseased states, aging, across individuals). Recent experimental evidence further suggests that the adverse effect of lesions is visible on spontaneous dynamics characterized by changes in resting state functional connectivity and its graph theoretical properties (e.g. modularity). These changes originate from altered neural dynamics in individual brain areas that are otherwise poised towards a homeostatic equilibrium to maintain a stable excitatory and inhibitory activity. In this work, we employ a homeostatic inhibitory mechanism, balancing excitation and inhibition in the local brain areas of the entire cortex under neurological impairments like lesions to understand global functional recovery (across brain networks and individuals). Previous computational and empirical studies have demonstrated that the resting state functional connectivity varies primarily due to the location and specific topological characteristics of the lesion. We show that local homeostatic balance provides a functional recovery by re-establishing excitation-inhibition balance in all areas that are affected by lesion. We systematically compare the extent of recovery in the primary hub areas (e.g. default mode network (DMN), medial temporal lobe, medial prefrontal cortex) as well as other sensory areas like primary motor area, supplementary motor area, fronto-parietal and temporo-parietal networks. Our findings suggest that stability and richness similar to the normal brain dynamics at rest are achievable by re-establishment of balance.

Previous computational models have related spontaneous resting-state brain activity with local excitatory−inhibitory balance in neuronal populations. However, how underlying neurotransmitter kinetics associated with E-I balance governs resting state spontaneous brain dynamics remains unknown. Understanding the mechanisms by virtue of which fluctuations in neurotransmitter concentrations, a hallmark of a variety of clinical conditions relate to functional brain activity is of critical importance. We propose a multi-scale dynamic mean field model (MDMF) – a system of coupled differential equations for capturing the synaptic gating dynamics in excitatory and inhibitory neural populations as a function of neurotransmitter kinetics. Individual brain regions are modelled as population of MDMF and are connected by realistic connection topologies estimated from Diffusion Tensor Imaging data. First, MDMF successfully predicts resting-state functionalconnectivity. Second, our results show that optimal range of glutamate and GABA neurotransmitter concentrations subserve as the dynamic working point of the brain, that is, the state of heightened metastability observed in empirical blood-oxygen-level dependent signals. Third, for predictive validity the network measures of segregation (modularity and clustering coefficient) and integration (global efficiency and characteristic path length) from existing healthy and pathological brain network studies could be captured by simulated functional connectivity from MDMF model.

Precise estimates of epileptogenic zone networks (EZNs) are crucial for planning intervention strategies to treat drug-resistant focal epilepsy. Here, we present the virtual epileptic patient (VEP), a workflow that uses personalized brain models and machine learning methods to estimate EZNs and to aid surgical strategies. The structural scaffold of the patient-specific whole-brain network model is constructed from anatomical T1 and diffusion-weighted magnetic resonance imaging. Each network node is equipped with a mathematical dynamical model to simulate seizure activity. Bayesian inference methods sample and optimize key parameters of the personalized model using functional stereoelectroencephalography recordings of patients’ seizures. These key parameters together with their personalized model determine a given patient’s EZN. Personalized models were further used to predict the outcome of surgical intervention using virtual surgeries. We evaluated the VEP workflow retrospectively using 53 patients with drug-resistant focal epilepsy. VEPs reproduced the clinically defined EZNs with a precision of 0.6, where the physical distance between epileptogenic regions identified by VEP and the clinically defined EZNs was small. Compared with the resected brain regions of 25 patients who underwent surgery, VEP showed lower false discovery rates in seizure-free patients (mean, 0.028) than in non–seizure-free patients (mean, 0.407). VEP is now being evaluated in an ongoing clinical trial (EPINOV) with an expected 356 prospective patients with epilepsy.